Discovery of novel complex III inhibitor by docking-based virtual screening

In order to discover better inhibitors of the complex III, 14 compounds were selected from the Specs database by the gradual filtering method and their antifungal activities in vitro were evaluated. The results showed that, at the concentration of 50 μg/mL, all of the 14 compounds exhibited the fungicidal activities against 5 phytopathogenic fungi, in cluding Sclerotinia sclerotiorum, Rhizoctonia solani, Phytophthora infestans, Fusarium oxysporum f. sp. vasinfectum and Botrytis cinerea. Among those 14 compounds, compound 9 against better activity than the commonly used fungicide azoxystrobin, and the EC₅₀ value of the compound 9 against the aforementioned phytopathogenic fungi were 8.42, 74.89, 80.64, 96.17 and 32.94 μg/mL, respectively. To further investigate the molecular mechanism of compound 9 , the molecular docking and molecular dynamics simulation were conducted. The result showed the compound 9 and azoxystrobin had similar binding conformation and both of them formed a hydrogen bond with Glu(C271) in the active site. This study on compound 9 provides more insight into the molecular mechanism of the complex III inhibition and sets the foundation for future researches.